Our primary interest is in control mechanisms. We have been working in three major areas: 1) Super controls in the cell. We have been studying cyclic AMP, guanosine-tetra-phosphate, nucleotide and phosphate control in Salmonella. We are trying to generalize the ideas on super connrols that have come out of the study of cyclic AMP. 2) Control of the histidine operon. We have shown that histidyl-tRNA is an essential molecule in the control mechanism and we are studying the tRNA, synthetase, and other proteins in order to understand the mechanism of this control. We have developed a cell free system and have succeeded in making histidine biosynthetic enzymes in vitro and showing that this system is under control. We will now try to isolate the various components of this control. 3) We have found mutants that are lacking a pseudouridine in tRNA and that are derepressed for histidine biosynthesis, and leucine, isoleucine, and valine biosynthesis. We are investigating the role of this conversion in control mechanisms for amino acid operons. BIBLIOGRAPHIC REFERENCES: Stephens, J.C., Artz, S.W. and Ames, B.N. (1975) Guanosine-5'-diphosphate-3'-diphosphate (ppGpp): A positive effector for histidine operon transcription and a general signal for amino acid deficiency. Proc. Nat. Acad. Sci. USA 72, 4389-4393.